Genetic and biochemical experiments have shown that the product of the Rous sarcoma virus src gene is required for the initiation and maintenance of cellular transformation. As a part of our long-term goal of understanding how the src gene product, pp60src, mediates the molecular events involved in cellular transformation, we have isolated and partially characterized monoclonal antibodies directed against pp60src. The experiments outlined in this proposal employ monoclonal antibodies to unique determinants within pp60src as immunochemical probes to define and characterize the structural and functional domains of the molecule and attempt to elucidate the role of individual functional domains in mediating cellular transformation. We further propose to utilize monoclonal antibodies to pp60src as immunochemical probes to compare the structure and function of other retrovirus tyrosine protein kinase as well as normal cell tyrosine protein kinases. These studies will permit us to define the structural and functional domains of pp60src and allow us to relate this information to other proteins which may be members of a family of related tyrosine protein kinases.